Cancer and Other Mortality Risks in a Cohort of U.S. Radiologic Technologists In 1982, the Radiation Epidemiology Branch (REB), in collaboration with the University of Minnesota, initiated a nationwide cohort study of cancer incidence and mortality among 146,022 U. S. radiologic technologists. The cohort is 73% female, offering a rare opportunity to study effects of protracted low- to moderate-dose radiation exposure on breast and thyroid cancer, the two most sensitive organ sites for radiation carcinogenesis in women. Other cancer and non-cancer serious disease outcomes are also being evaluated in relation to protracted low-to-moderate dose exposures. Major findings since 2001 include: Mortality risks for breast cancer increased significantly with increasing number of years worked before 1950; mortality from cerebrovascular diseases increased significantly with earlier year first worked and with number of years worked before 1950; significantly elevated risks were found for incident cancers of the breast (female), thyroid, and melanoma compared to SEER and adjusted for non-response. Internal cohort analyses revealed significantly elevated incidence risks for breast cancer associated with working before 1940, melanoma and non-melanoma skin cancers related to working before 1950, modest elevated risk for non-chronic lymphocytic leukemia related to working >5 years before 1950, and a suggested elevated risk for thyroid cancer with working before 1960, while no associations were found for lung cancer. Mutational analysis of ZBRK1 and BRIP1 genes revealed that mutations in these genes are unlikely to account for a significant fraction of inherited breast cancer; kin-cohort analyses of breast cancer among first-degree relatives found a non-significant elevated risk associated with HER2 variant status of probands, significantly increased risks associated with XRCC1 194 and BRIP1 919 variants, and significantly reduced risks associated with APEX 148 and BRCA2 372 variants. During the past year, a Version 1 dose assessment was completed, providing estimates of annual and cumulative occupational badge doses (personal dose equivalent) for each technologist for each year worked from 1916 through 1984, as well as absorbed doses to organs and tissues including bone-marrow, female breast, thyroid, ovary, testes, lung and skin. The annual doses are defined as density distributions to account for uncertainties in the estimates. In analyses adjusted for other major breast cancer risk factors, statistically significant linear dose-response relationships were found for breast cancer incidence with cumulative mean breast dose (ERR=2.32) and based on 100 Monte Carlo realizations of breast dose (ERR=3.96). During the coming year, a third follow-up survey will be conducted, the genetic studies will be expanded to incorporate a prospective biospecimen collection, and additional refinements will be made to the dose assessment. Cancer Mortality in Russian Nuclear Workers Exposed to Plutonium A cohort of 26,000 Mayak nuclear facility workers (in the former Soviet Union)is being studied because they comprise a unique occupational group for protracted exposure to external radiation at high doses, and exposure to plutonium. Analyses evaluating the effects of external radiation exposure showed dose-response relationships for leukemia and all solid cancers. Mortality analyses of the Mayak workers demonstrate that internal exposure to plutonium results in excess risk of bone and liver cancer, with higher risks for females than males. Analyses are underway that evaluate risk of lung, liver, and bone cancer as a function of doses to the organs. Leukemia and Other Cancer Incidence in Chornobyl Clean-Up Workers Several studies of Chornobyl clean-up workers are currently underway. Cancer incidence through 1998 is being evaluated in three cohorts, comprising 17,000 clean-up workers, from Estonia, Latvia, and Lithuania, who were sent to Chornobyl (Ukraine) following the reactor accident in 1986. In addition, with support from DOE and NRC, NCI is conducting a "nested" study of leukemia and other hematologic disease among the approximately 110,000 Chornobyl clean-up workers in Ukraine. Incidence of Breast and Other Cancers and Chromosome Aberrations in Flight Personnel A cancer incidence study is underway to determine whether female flight attendants are at increased risk of breast or other cancers due to cosmic radiation exposure. A biodosimetry study to assess cosmic radiation exposure will compare the induction and persistence of chromosome aberrations by fluorescence in situ hybridization (FISH) among 78 pilots compared with 50 university faculty with minimal flying experience.